1:IDIBAPS

CAR-T cell therapy has shown tremendous promise for the treatment of B-cell malignancies, marking a new era in cancer therapy. However, several challenges remain for successfully applying CAR-T cells to solid tumors and other hematologic malignancies. In order to enhance the therapeutic outcome of CAR-T cells it is important to design strategies to enhance T cell fitness, avoid tumor escape and control toxicities. Genome editing tools are a powerful platform to further optimize the activity of next generation CAR-T cells. Genome editing has been used to generate allogeneic ‘‘off-the-shelf’’ CAR-T cells, to eliminate detrimental genes for CAR-T cell development and function or to knockin the CAR or additional transgenes into desired loci of the T cell genome. Here, we will discuss some genome editing tools, protocols and strategies used to develop next generation CAR-T cells with improved therapeutic index.